Project Summary We propose to develop a novel volumetric specimen imager (VSI) system for significantly reducing breast lumpectomy?s reoperation rate and improving cosmetic outcomes. Among the annual performance of >200,000 lumpectomies in the US, about 25% of patients need reoperations, when post-surgery pathology examination reveals ?positive margin?, indicating incomplete tumor removal in initial surgery. Currently physicians rely either on 2D intra-operative specimen imaging, which has only ~53% sensitivity for positive margin detection, or on randomly shaving additional cavity tissues at all margins, leading to 50% higher excision volume and worse cosmetic outcome. We propose a robust VSI system that yields fully-3D images of the specimen with isotropic, sub-100m resolution, and workflow-streamlining software applications which can significantly improve margin assessment and enable precisely image-guided shave margin. Uniquely enabled by a proprietary algorithm invented by Clarix founders, the VSI provides superior image quality meeting clinical requirements and significant imaging acceleration for seamless workflow integration. In 4-5 years, we plan to introduce the VSI-based solution as the new standard of care for lumpectomy, which is expected to lower the reoperation rate to <10% while reducing excision volume by 30%, thereby considerably reducing healthcare costs and patient inconvenience while improving cosmetic outcomes. We have successfully achieved all Aims in Phase I study, which include (1) to verify that image-quality requirements can be met by a calibrated VSI prototype, (2) to verify that scan-time requirements can be met by optimizing VSI parameters, and (3) to verify that VSI has 90% sensitivity and specificity for assessing lumpectomy margins. In our Phase II study, we hypothesize that an optimized, manufacture-ready VSI prototype can meet technical, workflow, and regulatory requirements for clinical application, and can result in substantially improved margin-assessment accuracy and breast-tissue conservation. The Specific Aims are: (1) to optimize VSI device for robust image acquisition in OR, (2) to create VSI software for seamless OR workflow integration, and (3) to conduct clinical VSI validation for enhancing margin-assessment accuracy and reducing cavity shave-margin volume. Currently 6,000 hospitals and clinics performing lumpectomy in the US form a $720M installed-base. We will focus our in-house talent on the core software and configuration design. We will partner with experienced specialists for regulatory-compliant engineering design, and with leading research hospitals for clinical study. Our Phase I success has attracted investors such as Softbank for assisting to obtain FDA 510(k) clearance within 2 years. After proving the commercial viability regionally, we will obtain further venture financing to scale nationally and internationally.